Galectin-7 is a beta-galactoside-binding animal lectin initially identified as a differentiation marker expressed in all types of stratified epithelia as well as a protein that is down modulated in SV-40 transformed keratinocytes. This protein has been found to be induced by p53 in a colorectal carcinoma cell line and designated as PIG1 (p53-induced gene-1). Our work has focused on the proapoptotic function of this protein, with an ultimate goal of developing a therapeutic approach to squamous cell carcinoma. We have studied the signaling pathway by which galectin-7 activates apoptotic function and found that JNK activation and mitochondrial cytochrome c release are responsible for the action mediated by galectin-7. Inducing activation of galectin-7 up-regulates differentiation- as well as apoptosis-related genes. Expressing this protein in colorectal carcinoma cells profoundly suppressed their tumor growth in vivo, indicating the potential for developing galectin-7 into strategy for cancer therapy. In this research proposal we will study: 1. Investigation of the effect of galectin-7 on cell growth and apoptosis in normal human keratinocytes: We will extend our previous mechanistic analysis on galectin-7's proapoptotic and growth-suppressive functions to the studies using normal human keratinocytes. For this, the gene knock-down approach using a short interfering RNA system will be pursued and various aspects of apoptosis will be analyzed. 2. Investigation of the antitumor functions of galectin-7 in squamous cell carcinoma: We will analyze galectin-7 expression in SCC specimens as well as cell lines with different degree of malignancy. Then, we will investigate galectin-7's potential impact on SCC by transfecting the galectin-7 gene into a SCC line and in vitro cell growth, apoptosis, and in vivo tumor growth will be evaluated.